Open Access Research BMJ Open: first published as 10.1136/bmjopen-2017-020673 on 5 May 2018. Downloaded from Short-term abstinence from alcohol and changes in cardiovascular risk factors, liver function tests and cancer-related growth factors: a prospective observational study Gautam Mehta,1 Stewart Macdonald,1 Alexandra Cronberg,2 Matteo Rosselli,1 Tanya Khera-Butler,2 Colin Sumpter,2 Safa Al-Khatib,1 Anjly Jain,3 James Maurice,1 Christos Charalambous,1 Amir Gander,4 Cynthia Ju,5 Talay Hakan,6 Roy Sherwood,7 Devaki Nair,8 Rajiv Jalan,1 Kevin P Moore1 To cite: Mehta G, Macdonald S, ABSTRACT Strengths and limitations of this study Cronberg A, et al. Short-term Objective To assess changes in metabolic risk factors and abstinence from alcohol and cancer-related growth factors associated with short-term changes in cardiovascular ► Prospective study design. abstinence from alcohol. risk factors, liver function ► Recruitment of a control group. Design Prospective, observational study. tests and cancer-related ► Thorough characterisation of the biological and life- growth factors: a prospective Setting Single tertiary centre. style confounders. Participants Healthy subjects were recruited based observational study. BMJ Open ► Lack of randomisation to groups. 2018;8:e020673. doi:10.1136/ on intention to: (1) abstain from alcohol for 1 month ► Study cohort all from university teaching hospital or bmjopen-2017-020673 (abstinence group), or (2) continue to drink alcohol science magazine. (control group). Inclusion criteria were baseline alcohol ► Prepublication history and additional material for this consumption >64 g/week (men) or >48 g/week (women). paper are available online. To Exclusion criteria were known liver disease or alcohol risk of metabolic diseases such as type 2 diabetes and view these files, please visit dependence. fatty liver disease. http://bmjopen.bmj.com/ the journal online (http:// dx. doi. Primary and secondary outcome measures The org/ 10. 1136/ bmjopen- 2017- primary outcome was change in insulin resistance 020673). (homeostatic model assessment (HOMA) score). Secondary INTRODUCTIOn outcomes were changes in weight, blood pressure (BP), Received 16 November 2017 Alcohol is a major cause of disability and vascular endothelial growth factor (VEGF), epidermal Revised 2 March 2018 preventable death. Globally, alcohol is the Accepted 5 April 2018 growth factor (EGF) and liver function tests. Primary and secondary outcomes were adjusted for changes in diet, seventh leading risk factor overall in terms of exercise and cigarette smoking. disability-adjusted life years (DALYs), and is Results The abstinence group comprised 94 participants the leading risk factor globally in working age on September 27, 2021 by guest. Protected copyright. (mean age 45.5 years, SD ±1.2) and the control group individuals (ages 15–59). Moreover, alcohol 47 participants (mean age 48.7 years, SD ±1.8). Baseline use-attributable DALYs have increased by over alcohol consumption in the abstinence group was 25% in the last 25 years.1 European countries 258.2 g/week, SD ±9.4, and in the control group 233.8 g, have among the highest alcohol consump- SD ±19.0. Significant reductions from baseline in the tion. Eastern Europe has the highest per abstinence group (all p<0.001) were found in: HOMA score capita consumption worldwide,2 and in the (−25.9%, IQR −48.6% to +0.3%), systolic BP (−6.6%, UK over 25% of the adult population drink IQR −11.8% to 0.0%), diastolic BP (−6.3%, IQR −14.1% in excess of recommended guidelines.3 to +1.3%), weight (−1.5%, IQR −2.9% to −0.4%), VEGF Aside from liver disease, which is the third (−41.8%, IQR −64.9% to −17.9%) and EGF (−73.9%, most common cause of preventable death IQR −86.1% to −36.4%). None of these changes were in the UK, there is also a significant burden associated with changes in diet, exercise or cigarette from alcohol-related cancer and meta- smoking. No significant changes from baseline in primary 3 or secondary outcomes were noted in the control group. bolic syndrome. Alcohol has been classi- For numbered affiliations see Conclusion These findings demonstrate that abstinence fied by the WHO as a class I carcinogen for end of article. from alcohol in moderate–heavy drinkers improves insulin some decades, and a report from the World Correspondence to resistance, weight, BP and cancer-related growth factors. Cancer Research Fund/American Insti- Dr Gautam Mehta; These data support an independent association of alcohol tute for Cancer Research states that there is gautam. mehta@ ucl. ac. uk consumption with cancer risk, and suggest an increased convincing evidence that alcohol is causally Mehta G, et al. BMJ Open 2018;8:e020673. doi:10.1136/bmjopen-2017-020673 1 Open Access BMJ Open: first published as 10.1136/bmjopen-2017-020673 on 5 May 2018. Downloaded from related to cancers of the oral cavity, pharynx, larynx, AUDIT questionnaire (modified to capture data for the oesophagus, breast and colorectum.4 preceding 6–8 months). Moreover, it has long been recognised that there is Sample size calculation for the control group was an important interaction between alcohol misuse and performed, based on pre/post data acquired from the fatty liver disease.5 One of the main factors driving the abstinence group (table 1). Specifically, based on these development of fatty liver disease and steatohepatitis is data, a power calculation determined that the following insulin resistance. Thus, any action that improves insulin sample sizes were required to detect statistically signifi- resistance will have a major impact on the development cant differences of the same magnitude (80% power, and severity of fatty liver disease. However, there remains alpha 5%, two-sided test): HOMA score n=47, weight debate as to the impact of alcohol consumption on fatty n=21, VEGF n=31, EGF n=30. liver disease driven predominantly by insulin resistance BP was measured seated, following a 2 min rest period, and metabolic factors.6 7 and the mean of three measurements was recorded. In this climate of increased awareness of alcohol-re- Fasting blood was taken, between 08:00 and midday, for lated morbidity, the UK Chief Medical Officers have measurement of glucose, insulin, liver function tests, revised downwards their weekly guidance limits.8 Addi- lipids, carbohydrate deficient transferrin (abstinence tionally, public health campaigns, where non-dependent group only) and VEGF (isoforms 165, 145 and 121) and drinkers are encouraged to commit to short-term absti- EGF (Randox Investigator, Randox, Belfast, UK). The nence from alcohol, are increasingly common. The aim HOMA score was calculated according to the methods of this study was to assess changes in insulin resistance, of Matthews et al.11 Participants with diabetes requiring metabolic risk factors and cancer-related growth factors treatment were excluded from HOMA measurements. with short-term abstinence from alcohol in moderate drinkers. Statistical analysis Baseline and 1-month differences were analysed by paired t-test for normally distributed differences in METHODS continuous variables, by Wilcoxon signed-rank test for Study design non-normally distributed differences in continuous 2 This was a single-centre, prospective, observational study variables, and differences in categorical variables by Χ conducted at the Royal Free London NHS Foundation test. Differences between abstinence and control groups Trust. Written informed consent was obtained from all were analysed by unpaired t-test for normally distributed participants. Study recruitment was initiated through email variables, and Mann-Whitney test for variables that were advertising within University College London, Queen Mary not normally distributed. Lifestyle factors were categor- University of London and New Scientist Magazine. The ically graded (better/same/worse), and delta change in http://bmjopen.bmj.com/ entry criteria were baseline alcohol consumption of >64 g/ biological variables between lifestyle groups was assessed week (eight units) for men or >48 g/week (six units) for by Kruskal-Wallis test. Multivariable logistic regression women. Exclusion criteria were >3 days abstinence from analysis was also used to test the effect of abstinence on alcohol prior to commencement of the study, the presence improvement in HOMA, weight, BP, VEGF and EGF once of known liver disease or alcohol dependence. Participants other lifestyle factors (diet and exercise) were taken into were not randomised to group, but were allocated based account. Correlation between biological variables was on intention to maintain abstinence for 1 month (absti- assessed by Spearman’s correlation. All analyses were nence group) or to continue alcohol consumption (control performed using STATA V.13.1 and SPSS Statistics V.21.0. on September 27, 2021 by guest. Protected copyright. group). SD is reported for means and IQR for medians where Participants were assessed at baseline, and after 1 month. applicable. All p values are two sided; p<0.01 was consid- The primary outcome was change in insulin resistance ered significant to account for multiple comparisons. (homeostatic model assessment (HOMA) score) at base- Patient and public involvement line and 1 month. Secondary outcomes were changes in The research question was developed following public weight, blood pressure (BP), vascular endothelial growth feedback to a pilot project, conducted in collaboration factor (VEGF), epidermal growth factor (EGF) and liver with, and published by, New Scientist magazine (New function tests. Information on diet, exercise and smoking Scientist, 31 December 2013). Additionally, the research history were obtained by self-reporting using components question was informed by focus groups, funded through of the Simple Lifestyle Indicator Questionnaire (SLIQ).9 the National Institute for Health Research Enabling Self-reported alcohol intake was assessed at baseline Involvement Fund. No specific patient advisers were using the full Alcohol Use Disorders Identification Test involved in the design or conduct of the study. Results of (AUDIT) questionnaire, and a direct interview by a single the study will be disseminated to all participants by email.